The goal of our proposed research is to use high-intensity, short-pulse lasers to accelerate protons to a therapeutic energy of 230 MeV. The successful completion of this critical goal would open the door to the development of a laser-accelerator that would replace standard modes of proton acceleration. This would potentially allow the dosimetric advantages of proton therapy to become available in a cost-effective manner for general use in the management of cancer. While theoretical results indicate that therapeutic energies are attainable, the critical issue is to experimentally deliver a sufficient intensity to a thin target without creating an excessive preplasma or compromising the physical integrity of the rear target surface. This requires a very high laser contrast, which is defined as the ratio of the intensities of the main pulse and a weaker prepulse, which is a feature of these lasers. The specific aims of this proposal are 1) to accelerate protons to therapeutic energies, and 2) conduct theoretical simulations to guide experimental procedure, refine theoretical models, and confirm our understanding of laser-based proton acceleration mechanisms. This will be the first study using laser intensities which are predicted to yield protons of therapeutic energies. In our proposed method, we will use "frequency-doubling" to improve the contrast to eliminate preplasma effects and systematically study a series of 2D parameter spaces to determine the effect of laser intensity and target thickness on proton energy using several different targets. The maximum resulting proton energy would be measured, using time-of-flight and a spectrometer, and correlated to these two variables for several different targets. Regions of parameter space resulting in greater proton energies will be studied in greater detail. Theoretical simulations will guide experimental work, while themselves being refined based on experimental results. Over the past 50 years, proton therapy has been shown to give similar or better local control of cancer than X-ray therapy. However, because it costs more than ten times as much, it is not widely available. This research will conduct the first critical step in determining if the cost can be dramatically reduced through the use of new acceleration technology. [unreadable] [unreadable] [unreadable]